CN112807321B - 治疗脑缺血再灌注损伤的组合物及其应用 - Google Patents
治疗脑缺血再灌注损伤的组合物及其应用 Download PDFInfo
- Publication number
- CN112807321B CN112807321B CN202110052551.2A CN202110052551A CN112807321B CN 112807321 B CN112807321 B CN 112807321B CN 202110052551 A CN202110052551 A CN 202110052551A CN 112807321 B CN112807321 B CN 112807321B
- Authority
- CN
- China
- Prior art keywords
- composition
- cerebral ischemia
- reperfusion injury
- alpha
- nmn
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 52
- 206010008118 cerebral infarction Diseases 0.000 title claims abstract description 26
- 201000006474 Brain Ischemia Diseases 0.000 title claims abstract description 24
- 206010008120 Cerebral ischaemia Diseases 0.000 title claims abstract description 24
- 206010063837 Reperfusion injury Diseases 0.000 title claims abstract description 17
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 claims abstract description 18
- FZAQROFXYZPAKI-UHFFFAOYSA-N anthracene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC3=CC(S(=O)(=O)Cl)=CC=C3C=C21 FZAQROFXYZPAKI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000003188 neurobehavioral effect Effects 0.000 claims abstract description 9
- 208000006011 Stroke Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000002775 capsule Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000010410 reperfusion Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 229960004788 choline alfoscerate Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 241000700159 Rattus Species 0.000 abstract description 23
- 230000000694 effects Effects 0.000 abstract description 13
- DAYLJWODMCOQEW-TURQNECASA-N NMN zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)([O-])=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-N 0.000 description 20
- 230000000324 neuroprotective effect Effects 0.000 description 11
- 210000001168 carotid artery common Anatomy 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 235000013305 food Nutrition 0.000 description 9
- -1 gui Paji Chemical compound 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 8
- 208000026106 cerebrovascular disease Diseases 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 235000013376 functional food Nutrition 0.000 description 8
- 230000000302 ischemic effect Effects 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 206010008190 Cerebrovascular accident Diseases 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 210000000269 carotid artery external Anatomy 0.000 description 5
- 230000002490 cerebral effect Effects 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- KSMRODHGGIIXDV-YFKPBYRVSA-N N-acetyl-L-glutamine Chemical compound CC(=O)N[C@H](C(O)=O)CCC(N)=O KSMRODHGGIIXDV-YFKPBYRVSA-N 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 229960005488 aceglutamide Drugs 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 239000007909 solid dosage form Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000006189 buccal tablet Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000004090 neuroprotective agent Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 2
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010011086 Coronary artery occlusion Diseases 0.000 description 2
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 2
- 240000001624 Espostoa lanata Species 0.000 description 2
- 235000009161 Espostoa lanata Nutrition 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DDNCQMVWWZOMLN-IRLDBZIGSA-N Vinpocetine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(=O)OCC)N5C2=C1 DDNCQMVWWZOMLN-IRLDBZIGSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 208000013404 behavioral symptom Diseases 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 210000004004 carotid artery internal Anatomy 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000001627 cerebral artery Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 229960001284 citicoline Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000249 desinfective effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 2
- 229950009041 edaravone Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 2
- 229960002435 fasudil Drugs 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 235000020256 human milk Nutrition 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 2
- 229960002497 nicorandil Drugs 0.000 description 2
- 229960000715 nimodipine Drugs 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000036284 oxygen consumption Effects 0.000 description 2
- 229960001476 pentoxifylline Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229960000744 vinpocetine Drugs 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- ZHAKAIBZKYHXJS-UHFFFAOYSA-N 2-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=NC=CS1 ZHAKAIBZKYHXJS-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 235000003276 Apios tuberosa Nutrition 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- PCLITLDOTJTVDJ-UHFFFAOYSA-N Chlormethiazole Chemical compound CC=1N=CSC=1CCCl PCLITLDOTJTVDJ-UHFFFAOYSA-N 0.000 description 1
- 208000004481 Choline Deficiency Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 229940123511 Excitatory amino acid receptor antagonist Drugs 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 244000133018 Panax trifolius Species 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 240000007164 Salvia officinalis Species 0.000 description 1
- 229940127505 Sodium Channel Antagonists Drugs 0.000 description 1
- 229940089973 Sodium channel antagonist Drugs 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 208000021752 choline deficiency disease Diseases 0.000 description 1
- 210000003109 clavicle Anatomy 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 229960004414 clomethiazole Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 230000009193 crawling Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 244000013123 dwarf bean Species 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 1
- 229940107187 fructooligosaccharide Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 235000021331 green beans Nutrition 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 208000037907 haemorrhagic injury Diseases 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 229960002310 pinacidil Drugs 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 235000005412 red sage Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/13—Nucleic acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供治疗脑缺血再灌注损伤的组合物，其包含β‑烟酰胺单核苷酸(NMN)和L‑α‑甘油磷酸胆碱(α‑GPC)，其中，按照L‑α‑甘油磷酸胆碱的使用剂量为15～25mg/kg/d、β‑烟酰胺单核苷酸的使用剂量为10～30mg/kg/d给药。在经典的MCAO模型中，本发明组合物对人工造模后MCAO大鼠的神经行为学有着改善作用。
Description
技术领域
本发明涉及一种治疗脑缺血再灌注损伤的组合物及其应用。
背景技术
脑中风是一组以脑部缺血及出血性损伤症状为主要临床表现的疾病，又称脑卒中或脑血管意外，具有极高的病死率和致残率，主要分为出血性脑中风(脑出血或蛛网膜下腔出血)和缺血性脑中风(脑梗塞、脑血栓形成)两大类，其中，以脑梗塞最为常见。脑中风发病急，病死率高，是世界上最重要的致死性疾病之一。脑是人类的重要器官之一，其重量仅为体重的2％，但其耗氧量则占全身耗氧量的20％，其所需血供占心输出量的15％，因此对氧和血的要求特别高，极易受到缺血性损害，其中由大脑中动脉梗塞造成的脑缺血尤为常见。中华人民共和国卫生部官方网站提供的统计数据显示，2003年脑血管疾病在城市和农村疾病死亡原因中均排名第二位，仅次于恶性肿瘤。脑血管病包括缺血性和出血性脑血管病，其中缺血性脑血管病占80～85％。
中风的死亡率也有随年龄增长而上升的趋势，由于一直缺乏有效的治疗措施，目前认为预防是最好的措施，因此，加强对全民普及脑中风的危险因素及先兆症状的教育，才会真正获得有效的防治效果。然而天有不测风云，罹患中风的病患如何更好的康复一直备受关注，脑中风，特别是缺血性脑中风之后的神经保护、神经修复类医药也是医药界重要的研究课题。目前神经保护剂分为以下几类：(1)离子通道调节剂：如钙离子通道拮抗剂尼莫地平、桂派齐特、法舒地尔；钠离子通道拮抗剂长春西汀；钾离子通道激活剂吡那地尔、尼可地尔、色满卡林。(2)作用于细胞水平的脑保护剂 (稳定细胞膜和提供能量)：如胞磷胆碱、三磷酸胞苷、小牛血清提取物、己酮可可碱。(3)兴奋性氨基酸受体拮抗剂：如神经节苷脂、醋谷胺(乙酰谷酰胺)。(4)γ- 氨基丁酸(GABA)受体激动剂：如氯美噻唑。(5)自由基清除剂与抗氧化剂：如依达拉奉。(6)其他神经保护剂：如中药制剂丹参、刺五加等，以及一氧化氮合酶抑制剂、神经营养因子、腺转运抑制剂等。然而，仍需要开发更多的安全有效的治疗脑缺血再灌注损伤的药物。
发明内容
本发明的目的是开发一款可以适合长期服用并能够预防或改善脑缺血再灌注损伤组合物。本发明的发明人经过深入研究，意外地发现将NMN和α-GPC组合使用，显示了脑缺血再灌注损伤的改善作用，从而完成了本发明。本发明的组合物，可以应用于制备用于治疗脑缺血再灌注损伤的药物，或者以预防和治疗为目的功能性食品。
具体而言，本发明提供一种具有神经保护作用的组合物，其特征在于，其包含 L-α-甘油磷酸胆碱(α-GPC)和β-烟酰胺单核苷酸(NMN)，其中，β-烟酰胺单核苷酸的使用剂量为10～30mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为15～25mg/kg/d。
作为本发明优选实施方式的药物制剂，可以为片剂、胶囊剂。
本发明还提供一种功能性食品，包含上述的具有神经保护作用的组合物以及可食用的辅料。
本发明的组合物，可以应用于制备用于治疗脑缺血再灌注损伤的药物。
本发明中的α-GPC是L-α-甘油磷酸胆碱的简称，其是具有由构成细胞膜的主要磷脂PC(磷脂酰胆碱)脱去2个脂肪酸后的水溶性物质，原本在生物体内广泛存在，是存在于人的母乳及体液肿的身体成分之一，2009年的食品药品分类修订中，将L-α- 甘油磷酸胆碱(有时也可以称为sn-甘油-3-磷酸胆碱)定义为食品。α-GPC为可以通过血脑屏障少数几种营养素之一，因此可以迅速的从胆碱转换为乙酰胆碱，被认为是防止胆碱缺乏、增加神经递质、促进促生长激素的分泌等的营养素。然而，可能是由于单纯的摄入α-GPC营养品由于机体的调控作用，目前为止尚没有α-GPC的摄入能够治疗或者改善脑缺血导致的神经损伤的症状的报道。
NMN(Nicotinamide mononucleotide)是β-烟酰胺单核苷酸的简称，人体细胞中天然存在，为辅酶1NAD+的前体。可适当延长寿命。真正发挥抗衰老作用的是一种称为烟酰胺腺嘌呤二核苷酸(NAD+)的重要能量代谢物。NMN是一种营养物质，市场上可以获得商品。NMN会在细胞中转化为NAD+，它归类为一种全新的维生素B3，且超越了普通维生素的功效，被认为是预防衰老和恢复年轻的补充剂。NMN本身是人体内含有的物质，存在于母乳及食物中，例如毛豆、西兰花、黄瓜、圆白菜、鳄梨、番茄等，但含量非常少(每100克中含有0.25-1.88毫克)。生牛肉和虾等也含有非常少量的(每100克中含有0.06-0.42毫克)NMN成分。所以想要提高NMN，还要从外界直接补充。NMN一般认为主要通过:增加高密度脂蛋白、减少低密度脂蛋白、被氧化、减轻巨噬细胞的炎症反应、减少粥样硬化斑块的形成、增加粥样硬化斑块的稳定性、减少斑块破裂,改善血流等上述方式来防治心血管疾病。但是迄今为止，尚无直接证据证实NMN的摄入能够治疗或者改善脑缺血导致的神经损伤的症状。
然而本发明的发明人意外地发现，将NMN和α-GPC这两种内源性的营养成分组合使用，在动物模型上显示了一定程度改善脑缺血导致的神经损伤的症状的作用，提示了NMN和α-GPC合用作为预防或具有神经保护作用的前景，具体可以参见实施例中的具体实施例。
作为本发明的优选的实施方式，本发明还提供一种具有神经保护作用的药物制剂，其包含上述组合物，还包含药学上可用接受的辅料。
本发明的组合物在使用时，优选制成口服给药的固体剂型来给药。作为用于口服给药的固体剂型包括胶囊剂、片剂、丸剂、散剂和颗粒剂。在这些固体剂型中，将组合物与至少一种常规惰性赋形剂(或载体)混合，如柠檬酸钠或磷酸二钙，或与下述成分混合：(a)填料或增容剂，例如，淀粉、乳糖、蔗糖、葡萄糖、甘露醇和硅酸； (b)粘合剂，例如，羟甲基纤维素、藻酸盐、明胶、聚乙烯基吡咯烷酮、蔗糖和阿拉伯胶；(c)保湿剂，例如，甘油；(d)崩解剂，例如，琼脂、碳酸钙、马铃薯淀粉或木薯淀粉、藻酸、某些复合硅酸盐、和碳酸钠；(e)缓溶剂，例如石蜡；(f)吸收加速剂，例如，季胺化合物；(g)润湿剂，例如鲸蜡醇和单硬脂酸甘油酯；(h)吸附剂，例如，高岭土；和(i)润滑剂，例如，滑石、硬脂酸钙、硬脂酸镁、固体聚乙二醇、十二烷基硫酸钠，或其混合物。胶囊剂、片剂和丸剂中，剂型也可包含缓冲剂。
固体剂型如片剂、糖丸、胶囊剂、丸剂和颗粒剂可采用包衣和壳材制备，如肠衣和其它本领域公知的材料。它们可包含不透明剂，并且，这种组合物中活性化合物的释放可以延迟的方式在消化道内的某一部分中释放。可采用的包埋组分的实例是聚合物质和蜡类物质。必要时，组合物也可与上述赋形剂中的一种或多种形成微胶囊形式。
用于口服给药的液体剂型包括药学上可接受的乳液、溶液、悬浮液、糖浆或酊剂。除了本发明组合物外，液体剂型可包含本领域中常规采用的惰性稀释剂，如水或其它溶剂，增溶剂和乳化剂，例知，乙醇、异丙醇、碳酸乙酯、乙酸乙酯、丙二醇、1,3- 丁二醇、二甲基甲酰胺以及油，特别是棉籽油、花生油、玉米胚油、橄榄油、蓖麻油和芝麻油或这些物质的混合物等。除了这些惰性稀释剂外，组合物也可包含助剂，如润湿剂、乳化剂和悬浮剂、甜味剂、矫味剂和香料。
除了本发明组合物外，悬浮液可包含悬浮剂，例如，乙氧基化异十八烷醇、聚氧乙烯山梨醇和脱水山梨醇酯、微晶纤维素、甲醇铝和琼脂或这些物质的混合物等。用于肠胃外注射的组合物可包含生理上可接受的无菌含水或无水溶液、分散液、悬浮液或乳液，和用于重新溶解成无菌的可注射溶液或分散液的无菌粉末。适宜的含水和非水载体、稀释剂、溶剂或赋形剂包括水、乙醇、多元醇及其适宜的混合物。
从服用方便角度考虑，本发明的组合物优选制成片剂或者胶囊剂。为制备本发明组合物的粉剂的片剂或胶囊，可将本发明组合物的粉剂与制剂载体混合，该载体为常用的制片剂组分，如玉米淀粉、蔗糖、山梨醇、脂肪酸、硬脂酸镁和其它药用稀释剂。
本发明的具有神经保护作用的组合物，可以与其他类的具有神经保护作用的药物合用。作为其他的神经保护的药物，可举出尼莫地平、桂派齐特、法舒地尔；钠离子通道拮抗剂长春西汀、吡那地尔、尼可地尔、色满卡林、胞磷胆碱、三磷酸胞苷、小牛血清提取物、己酮可可碱、神经节苷脂、醋谷胺(乙酰谷酰胺)、如氯美噻唑、依达拉奉等临床常见的药物。
本发明还提供一种功能性食品，包含上述的具有神经保护作用的组合物以及可食用的辅料。
由于本发明的组合物由于原料完全可食用，非常适合开发成功能食品，例如可制备成口含片、糖果、固体饮料、液体饮料形式的功能性食品。本发明的功能性食品，包含本发明的上述组合物和可食用的辅料，作为可以使用的符合相关标准的食品添加剂，例如符合中华人民共和国GB2760-2014标准的食品添加剂。
作为本发明的功能性食品的优选形式，可以举出口含片。将本发明的组合物制成口含片的方式没有特殊限制，可以使用公知的方法，例如，将本发明的组合物的造粒，添加可食用的辅料等混合，进行压片的过程。作为可食用的辅料，可以举出淀粉、蔗糖、甲基纤维素低聚果糖、茶粉、食盐、甜菊糖苷、山梨糖醇、维生素C 等，但不限于这些，只要是符合GB2760-2014或其他国家的相关食品标准的辅料均可以适当添加。
本发明的组合物为了利于食用、利于防止吸潮等目的，也可以包衣。从食品角度出发，优选使用海藻酸钠、黄原胶、阿拉伯胶等完全符合食品标准的辅料进行包衣。
作为本发明的功能性食品的优选形式，从食品化观感强，接受度高的角度考虑，本发明的组合物，还可以制成食品口服液的形式。作为食品口服的液体制剂的剂型有溶液、糖浆或混悬液。这些液体制剂的制备方法中，分散媒一般为水，非水溶性的赋形剂如杏仁油、油脂；作为药剂学上允许使用的填加剂包括如山梨醇、氢化食用油、甲基纤维素；还包括防腐剂如甲基或丙基P-酚；乳化剂如卵磷脂、阿拉伯橡胶：人工色素或甜味剂。
作为给药的剂量，应根据对象的年龄、体重、健康状况及剂型的不同而定。推荐的使用剂量为β-烟酰胺单核苷酸的使用剂量为10～30mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为15～25mg/kg/d。但是由于本发明的原料成分均有着很强的安全性，本领域的技术人员可以根据个体需要，适当增加各组分有效用量。优选的使用量为β-烟酰胺单核苷酸的使用剂量为20mg/kg/d，L-α-甘油磷酸胆碱20mg/kg/d。
本发明的发明人通过实验动物模型，验证了本发明的组合物的具有治疗脑缺血再灌注损伤的药效。具体而言，本研究中采用利用经典的大鼠MCAO模型验证本发明组合物的活性效果。所谓的MCAO(middle cerebral artery occlusion)模型是人工方法将大鼠或小鼠等试验的脑动脉栓塞，结合神经行为学评价，从而评价给药成分的效果的模型。单独利用NMN灌胃大鼠没有表现出行为学上的症状改善，同样地，单独利用α-GPC灌胃大鼠也未表现行为学上的症状改善。然而，当组合使用NMN和α-GPC 进行灌胃时，意外地发现对于MCAO模型大鼠表现出了行为学上的症状改善，提示了组合使用NMN和α-GPC具有预防或具有神经保护作用的应用前景。
本发明的组合物与现有技术相比，存在以下明显的优势：本发明所开发的组合物的原料均为食品，是效果明确、安全性令人信服的具有神经保护作用的组合物，本发明的组合物并采用科学的动物表型验证了确切的效果，考虑到其特别适合以满足可以适合长期服用，因此虽然其效果不强，用于预防神经保护症状仍然有着广阔的市场前景。
具体实施方式
以下结合具体的实施例对本发明进行进一步详细的描述，实施例仅仅是为了说明本发明技术方案的实例，并非为了对本发明的保护范围进行任何限定。
实施例1大鼠MCAO模型的建立
本发明中利用经典的大鼠MCAO模型验证本发明组合物的活性效果。所谓的MCAO(middle cerebral artery occlusion)模型是人工方法将大鼠或小鼠等试验的脑动脉栓塞。具体的建模方法参照如下所示。
造模流程：作为受试动物，使用SD大鼠，8周龄(250g-350g体重)雄性，购自北京维通利华实验动物公司。SD大鼠40只，适应性喂养1周后，每组8只，随机分为5组：sham组(假手术组，仅切开表皮不进行血管结扎)、模型组、NMN组(给药 NMN 20mg/kg/d)、α-GPC组(给药α-GPC 20mg/kg/d)、组合物(NMN20mg/kg/d和α -GPC 20mg/kg/d)组。除了sham组，其余各组均进行下述的手术建模。
造模过程为，准备眼科剪、弯镊1对、(动脉夹2)、止血钳2-3、缝合线、缝合针、棉球、75％酒精、生理盐水、注射器(1ml)、大鼠板，麻醉剂采用7％水合氯醛。将大鼠称重，0.5ml/100g麻醉剂进行麻醉。将大鼠用医用胶带固定于操作台上，颈部剃毛。MCAO栓线采用2434型号尼龙栓线(购自于北京西浓)。颈部酒精棉球消毒，眼科剪沿锁骨正中做竖向切口。分离皮下肌肉组织，找到肌肉下方有轻微搏动血管即为颈总动脉，钝性分离覆盖于颈总动脉上方的肌肉，分离出颈总动脉后，眼科镊小心分离伴行于颈总动脉的迷走神经，还需要分离干净动脉周围粘膜组织，分离出右侧颈总动脉(CCA)、颈内动脉(ICA)及颈外动脉(ECA)，靠尾部结扎颈总动脉(CCA)。再结扎颈外动脉(ECA)，两个结扎之间备线，打松结。在ECA剪开切口，插入尼龙线，致使大脑中动脉阻塞缺血。1.5小时后，用眼科镊夹住栓线固定处将栓线拔出至其头端，放开CCA丝线，剪去多余栓线，逐层缝合，消毒；假手术组仅剥离颈总动脉后立即缝合创口。
实施例2利用大鼠MCAO模型进行的神经行为学评价
上述手术后放回笼子，各组大鼠灌胃给与相应的受试药物，并给予充足饲料和水。手术24小时后，通过目视观察各组大鼠的神经行为学状况，依据longa 5分制量表统计各组大鼠神经行为学评分，各组大鼠脑神经行为学评分(平均值±标准差)汇总在表1中。
评分标准如下：
0分：活动基本正常，无明显神经病学症状；
1分：左侧前爪无法完全伸展；
2分：爬行时向左侧转圈；
3分：行走时向偏瘫侧倾倒；
4分：不能自动行走，有意识障碍；
5分：死亡。
表1各组大鼠脑神经行为学评分(平均值±标准差)
模型组、NMN组与α-GPC组，与假手术组比较，P<0.01；组合物组与模型组比较， P<0.05。组合物组显示了对于脑缺血再灌注模型大鼠，在神经行为学上的改善作用。提示其可能存在相应的神经保护效果，能够用于治疗脑缺血再灌注损伤。
实施例3TTC染色
取各组大鼠利用10％水合氯醛腹腔注射麻醉，迅速断头取脑。取缺血再灌注侧大脑半球中部，同位置切出6片2mm的切片，在暗室中，用2％氯化三苯基四氮唑(TTC) 染色15分钟，用10％福尔马林固定一夜，非缺血区呈玫瑰红色，拍摄照片，使用 Image-Pro Plus计算机软件进行图像处理，计算脑相对缺血面积，汇总在表2中。
表2各组大鼠脑相对缺血面积(平均值±标准差)
组合物组显示了较少的缺血区域，与其他组存在显著性差异。
本说明书中引用的所有出版物和专利文献引入本文作为参考，如同每个出版物或专利被分别明确指明引入本文作为参考。在不偏离本申请公开的实质和范围的情况下，可对本申请公开的各实施方案进行多种改变和用等同物替换。除非上下文中另有说明，否则本公开的实施方案的任何特征、步骤或实施方案都可以与任何其他特征、步骤或实施方案组合使用。最后应说明的是：以上所述的各实施例仅用于说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述实施例所记载的技术方案进行修改，或者对其中部分或全部技术特征进行等同替换；而这些修改或替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (6)
1.由β-烟酰胺单核苷酸NMN和L-α-甘油磷酸胆碱α-GPC构成的组合物在制备用于治疗脑缺血再灌注损伤的药物中的应用。
2.根据权利要求1所述的应用，所述脑缺血再灌注损伤为中风后遗症脑缺血再灌注损伤。
3.一种治疗脑缺血再灌注损伤的组合物，其特征在于，其包含L-α-甘油磷酸胆碱α-GPC和β-烟酰胺单核苷酸NMN，其中，β-烟酰胺单核苷酸的使用剂量为10～30mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为15～25mg/kg/d。
4.一种治疗脑缺血再灌注损伤的药物制剂，其特征在于，其包含权利要求3中所述的组合物，以及药学上可用接受的辅料。
5.根据权利要求4所述的药物制剂，其为片剂、胶囊剂。
6.权利要求3所述的组合物在制备用于改善脑缺血再灌注MCAO模型大鼠的神经行为学表现药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110052551.2A CN112807321B (zh) | 2021-01-15 | 2021-01-15 | 治疗脑缺血再灌注损伤的组合物及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110052551.2A CN112807321B (zh) | 2021-01-15 | 2021-01-15 | 治疗脑缺血再灌注损伤的组合物及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112807321A CN112807321A (zh) | 2021-05-18 |
| CN112807321B true CN112807321B (zh) | 2022-11-29 |
Family
ID=75869330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110052551.2A Active CN112807321B (zh) | 2021-01-15 | 2021-01-15 | 治疗脑缺血再灌注损伤的组合物及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112807321B (zh) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2016200507A1 (en) * | 2009-09-15 | 2016-02-18 | Cerulean Pharma Inc. | Treatment of cancer |
| CN102028681B (zh) * | 2009-09-24 | 2012-05-30 | 广州市众为生物技术有限公司 | 椒苯酮胺或其盐在制备预防/治疗脑病的药物中的用途 |
| AU2012347557A1 (en) * | 2011-12-09 | 2014-07-03 | Metabolon, Inc. | Biomarkers for kidney cancer and methods using the same |
| WO2017015660A1 (en) * | 2015-07-23 | 2017-01-26 | Salk Institute For Biological Studies | Prevention and treatment of aging and neurodegenerative diseases |
-
2021
- 2021-01-15 CN CN202110052551.2A patent/CN112807321B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN112807321A (zh) | 2021-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20030181353A1 (en) | Composition & use as analgesic, anti-inflammatory, wound healing agent, for treatment of heart conditions, assessment of heart function & tissue & cell protection & healing & reperfusion, mood disorders & symptoms & sequelae of menopause & for inducing unconsciousness, sleep & anesthesia | |
| US20080268066A1 (en) | Synergistic Formulation for Preventing and/or Treating Diabetes | |
| JP7161402B2 (ja) | ウロリチン化合物を含む組成物 | |
| CN110327374B (zh) | 一种用五谷虫制备的用于预防和/或治疗惊厥的药物组合物 | |
| CN104825873B (zh) | Egcg与竹叶黄酮的组合物及其制备方法和应用 | |
| JP2019182881A (ja) | 末梢神経障害の予防又は改善用組成物 | |
| CN110099691A (zh) | 玛卡组合物和使用方法 | |
| CN104840800B (zh) | 竹叶黄酮与γ-氨基丁酸的组合物及其制备方法和应用 | |
| CN108514109A (zh) | 麻醉术后专用型临床营养配方及其制备方法 | |
| CN112807321B (zh) | 治疗脑缺血再灌注损伤的组合物及其应用 | |
| JP2015528474A (ja) | 脳梗塞の予防及び治療のための薬の調製上の３−ｎ−ブチルイソインドリノンの応用 | |
| TWI776450B (zh) | 正丁基苯酞於促進脂肪褐變、以及預防或治療脂肪肝及相關肝病變之應用 | |
| CN112716969B (zh) | 治疗阿尔茨海默症的组合物及其制备方法、应用 | |
| MXPA01000973A (es) | Un nuevo agente analgesico antiinflamatorio y de cicatrizacion de heridas. | |
| US20220370511A1 (en) | Methods and compositions for enhancing overall health and longevity in mammals | |
| JPH09309840A (ja) | 抗脱毛症状剤 | |
| CN107156816B (zh) | 一种适用于早期糖尿病人群和代谢综合征人群的保健食品 | |
| JPWO2010087150A1 (ja) | 胃酸分泌抑制剤及びカリウムチャンネル阻害剤 | |
| US20230404945A1 (en) | Application of alpha-asarone in preparation of medicine for preventing or treating hemorrhagic stroke | |
| CN102526035B (zh) | 一种用于制备抗脑血管疾病药物的组合物 | |
| CN116492327B (zh) | (2s,6s)-2,6-二氨基庚二酸在制备抗产后抑郁药物中的应用 | |
| CN109350615A (zh) | 盐酸水苏碱在预防和治疗缺血性脑血管疾病的新用途 | |
| CN106727605B (zh) | 环维黄杨星d在制备预防或治疗缺血性脑卒中药物中的应用 | |
| JP4902349B2 (ja) | 筋ジストロフィー進行抑制組成物 | |
| KR et al. | Clinical Evaluation of an Ayurvedic Preparation “Sangfer” for the Treatment of Anemia in Pregnant Women: An Open-labeled Clinical Study |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |